Methylprednisolone Succinate

ADMINISTRATION ROUTES:

IV

ALTERNATIVE NAMES:

Solu-Medrol

ICU INDICATIONS:

1. Steroid responsive lung diseases
2. ARDS
3. Stevens-Johnson syndrome
4. Laryngeal oedema (pre-extubation)

PRESENTATION AND ADMINISTRATION:

IV:

40 mg/mL (Act-O-Vial), 125mg/2 mL (Act-O-Vial), 500 mg/4 mL (Act-O-Vial), 1 gm (+15.6 mL solv)

Note: also available as Depo-Medrol (methylprednisolone acetate) which is for intramuscular use only. For Intensive Care use, Solu-Medrol (methylprednisolone succinate) is the preferred preparation and is for intravenous use only. Do not administer the acetate preparation intravenously.

Directions for mixing Act-O-Vial:

1. Tap to ensure powder at base of vial and away from central stopper
2. Place Act-O-Vial on flat stable surface
3. Press down on plastic activator with palm of hand to forced diluent into lower compartment
4. Gently agitate to dissolve powder. DO NOT SHAKE THE VIAL
5. Remove plastic tab covering the centre of stopper
6. Wipe top of stopper with alcohol swab
7. Insert needle squarely through centre of stopper until tip is just visible
8. Invert vial and withdraw dose.

Directions for mixing other vial preparations:

Add 1 gm to 15.6 mL of supplied diluent provided to make a final 62.5 mg/mL. Gently agitate to dissolve powder.

Doses of up to 250 mg can be injected slowly by direct IV injection over at least 5 minutes.

Doses of 125 mg to 3 gm may be diluted in 50 mL of compatible IV fluid and administered over 30 minutes.

Cardiac arrhythmias, circulatory collapse or arrest have been reported with rapid administration of 500 mg given in less than 10 minutes.

When reconstituted with water for injection use immediately and discard any unused solution. Small volume dilutions (50-100 mL) are stable for 6 hours at room temperature. Large volume dilutions (250-1000 mL) are stable for 24 hours at room temperature.

Compatible in the following IV fluids: 0.9% Normal saline, 5% dextrose, glucose and sodium chloride.

DOSAGE:

IV:

Doses vary widely depending on indication and must be indivisualised to the disease, its severity and clinical response over the duration of treatment. The lowest dose possible should be used for the shortest period.

For ARDS:

1-2 mg/kg od, reducing over 2 weeks

Pneumocystis pneumonia

Days 1-5: 30 mg BD

Days 6-10: 30 mg OD

Days 11-12: 15 mg OD

Pulsed dosing for conditions unresponsive to standard treatment (e.g. SLE, glomerulonephritis, lupus nephritis)

250 mg od for 3-5 days

Prophylaxis for laryngeal oedema in high-risk patients pre-extubation

20 mg 4 hourly for 4 doses beginning 12 hours prior to planned extubation

Acute exacerbation of multiple sclerosis

500 mg to 1 gm OD for 3-7 days

DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:

Dose as in normal renal function

DOSAGE IN PAEDIATRICS:

Doses vary widely depending on indication and must be individualised to the disease, its severity and clinical response over the duration of treatment rather than age or weight. The lowest dose possible should be used for the shortest period but paediatric dosage should not be < 0.5 mg/kg every 24 hours.

ARDS:

1-2 mg/kg OD

Acute Asthma: Children <12 years

1-2 mg/kg day in 2 divided doses. Max dose 60 mg/day

Children ≥12 years

40-80 mg day in 2 divided doses

Status asthmaticus (all ages):

Load 2 mg/kg/dose then 0.5 - 1 mg/kg/dose QID

Immune thrombocytopenia (moderate to severe bleeding):

Pulse 30mg/kg/dose OD for 1-3 doses

Pneumocystis pneumonia:

Children <12 years

Days 1 to 7: 1 mg/kg/dose QID

Days 8 to 9: 1 mg/kg/dose OD

Days 10 to 11: 0.5 mg/kg/dose BD

Days 12 to 16: 1 mg/kg/dose OD

Children ≥12 years

Days 1 to 5: 30 mg BD

Days 6 to 10: 30 mg OD

Days 11 to 21: 15 mg OD

CLINICAL PHARMACOLOGY:

Methylprednisolone is a potent anti-inflammatory steroid synthesised in a laboratory. Methylprednisolone is a steroid. 1 mg methylprednisolone is equivalent to 5 mg hydrocortisone in glucocorticoid activity and 0.5 mg in mineralocorticoid activity.

CONTRAINDICATIONS:

1. The use of methylprednisolone sodium succinate sterile powder is contraindicated in premature infants because the 40/125/500 mg & 1 g vials and the accompanying diluent for the 500 mg and 2 g vials contain benzyl alcohol. Benzyl alcohol has been reported to be associated with a fatal 'gasping syndrome' in premature infants
2. Systemic fungal infections
3. Known hypersensitivity to the product and its constituents

WARNINGS:

In patients on corticosteroid therapy subjected to any unusual stress, increased dosage of rapidly acting corticosteroids before, during, and after the stressful situation is indicated. Corticosteroids may mask some signs of infection, and new infections may appear during their use.

PRECAUTIONS:

General:

Drug-induced secondary adrenocortical insufficiency may be minimised by gradual reduction of dosage. This type of relative insufficiency may persist for months after discontinuation of therapy. In any situation of stress occurring during that period, hormone therapy should be reinstituted. Since mineralocorticoid secretion may be impaired, salt and/or a mineralocorticoid should be administered concurrently.

There is an enhanced effect of corticosteroids on patients with hypothyroidism and in those with cirrhosis.

Psychic derangements may appear when corticosteroids are used, ranging from euphoria, insomnia, mood swings, personality changes, and severe depression, to frank psychotic manifestations. Also, existing emotional instability or psychotic tendencies may be aggravated by corticosteroids.

An acute myopathy has been observed with the use of high doses of corticosteroids, most often occurring in patients with disorders of neuromuscular transmission (such as myasthenia gravis), or in patients receiving concomitant therapy with neuromuscular blocking drugs). This acute myopathy is generalised, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevations of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.

Laboratory Tests:

No tests in addition to usual ICU tests are required

Drug/Laboratory Test Interactions:

None of note

IMPORTANT DRUG INTERACTIONS IN ICU:

Convulsions have been reported with concurrent use of methylprednisolone and cyclosporin. Drugs that induce hepatic enzymes such as phenobarbital, phenytoin and rifampin may increase the clearance of methylprednisolone and may require increases in methylprednisolone dose to achieve the desired response.

ADVERSE REACTIONS:

Fluid and Electrolyte Disturbances:

Sodium retention, potassium loss, fluid retention, hypokalemic alkalosis, congestive heart failure in susceptible patients, hypertension

Musculoskeletal:

Muscle weakness, aseptic necrosis of femoral and humeral heads, steroid myopathy, loss of muscle mass, pathologic fracture of long bones, severe arthralgia, osteoporosis, vertebral compression fractures, tendon rupture (particularly of the Achilles tendon)

Gastrointestinal:

Peptic ulcer with possible perforation and haemorrhage, abdominal distention, ulcerative oesophagitis, pancreatitis. Increases in alanine transaminase (ALT, SGPT), aspartate transaminase (AST, SGOT), and alkaline phosphatase have been observed following corticosteroid treatment. These changes are usually small, not associated with any clinical syndrome and are reversible upon discontinuation

Dermatologic:

Impaired wound healing, facial erythema, thin fragile skin, increased sweating, petechiae and ecchymoses, may suppress reactions to skin tests

Neurological:

Increased intracranial pressure with papilloedema (pseudo-tumour cerebri) usually after treatment, convulsions, vertigo, headache

Endocrine:

Development of Cushingoid state, menstrual irregularities, suppression of growth in children, decreased carbohydrate tolerance, secondary adrenocortical and pituitary unresponsiveness (particularly in times of stress, as in trauma, surgery or illness), manifestations of latent diabetes mellitus, increased requirements for insulin or oral hypoglycaemic agents in diabetics